This comparative effectiveness research proposal (Studies of Comparative Treatments for Retinal Vein Occlusion 2 [SC0RE2] Study) aims to support alternative treatment protocols for decreased vision due to macular edema secondary to central retinal vein occlusion (CRVO) based on results of recent randomized trials. This proposed study called the SCORE2 Comparative Trial (SCT) will determine if bevacizumab is non-inferior to aflibercept for the treatment of macular edema due to RVO. The non-inferiority margin will be set at an Early Treatment Diabetic Retinopathy Study visual acuity letter score of 5. The SCT will also provide insight into treatment regimens after the initial 6 months to determine if the frequency of intravitreal injections can be reduced in eyes that have responded well to treatment (which would represent a more cost-effective treatment regimen, with fewer risks to patients of injection-related adverse events and a lesser logistical treatment burden for patients and providers), and the impact of alternative treatment strategies (intravitreal dexamethasone) in eyes that have not responded well to initial treatment with anti-VEGF therapy. So, in addition to the primary aim of test for non-inferiority of bevacizumab to aflibercept in visual acuity outcome at Month 6 for eyes, secondary aims will investigate different dosing strategies after Month 6. In addition, secondary analyses will examine retinal thickening and other retinal outcomes based on SD-OCT and wide field fluorescein angiograms (within a subset of sites). The SCT will also add to our knowledge of the safety profile of these anti-vascular endothelial growth factor (anti-VEGF) medications. We propose to enroll 360 CRVO patients over a 24-month period, and follow for 13-months. This application is for The EMMES Corporation to serve as the Data Coordinating Center (DCC) for the SCT, with our primary focus to provide data management, statistical, and operational support over 5 years of support.